safety, tolerability, and clinical effects of twice-daily doses of cinacalcet (amg 073) in adults with primary hyperparathyroidism (hpt)

Conditions: Primary Hyperparathyroidism

Summary: the primary objectives were to assess the safety and tolerability of twice daily (bid) doses of 65 mg cinacalcet administered orally to adults with primary hpt.


Eligibility criteria:
inclusion criteria: * men or women ≥ 18 years old before beginning of screening * use, in the opinion of the principal investigator, effective contraceptive measures throughout the study * negative serum pregnancy test within 15 days before day 0 * plasma ipth concentration \> 45 pg/ml on at least 2 occasions (during the screening phase) at least 7 days apart * serum calcium concentration ≥ 11 mg/dl on 2 occasions (during the screening phase) at least 7 days apart * acceptable renal function, with an estimated creatinine clearance \> 50 ml/min as determined by the cockroft and gault equation * acceptable hepatic function, defined as serum aspartate transaminase (ast), alanine transaminase (alt), and total bilirubin ≤ 2 times the upper limit of normal (central laboratory's range) * laboratory test results within the central laboratory's normal range for hematology, coagulation, urinalysis, and clinical chemistry parameters not mentioned specifically in other inclusion/exclusion criteria * chest x-ray within the past 12 months, with no evidence of an active infectious, inflammatory, or malignant process * informed consent for participation in the study exclusion criteria: * any unstable medical condition requiring hospitalization within 30 days before day 0, or otherwise unstable condition in the judgment of the investigator * awaiting or scheduled for parathyroidectomy within 2 months after study day 0 * pregnant or nursing * received, within 21 days before day 0, therapy with systemic glucocorticoids (\> 5 mg/day prednisone or equivalent), lithium, tricyclic antidepressants (with the exception of amitriptyline and nortriptyline), thioridazine, haloperidol, flecainide, drugs with a narrow therapeutic index that are primarily metabolized by hepatic cytochrome p450 cyp 2d6, drugs that affect renal tubular calcium handling (ie, thiazide or loop diuretics), or calcitonin * dose changes in bisphosphonates, thyroid replacement therapy, selective estrogen receptor modulators (serms), or changes in daily doses of estrogen (greater than 0.75 mg) within 90 days before day 0 * subjects who discontinued estrogen or serm therapy must have been off treatment for at least 90 days before day 0. * alcohol or illicit drug abuse within 12 months before day 0 based on self-report * myocardial infarction within 6 months before day 0 * ventricular rhythm disturbance requiring current treatment * seizure within 12 months before day 0 * history (within 5 years) of malignancy of any type, other than nonmelanomatous skin cancers or in situ cervical cancer * evidence (within 5 years) of treatment for and/or active sarcoidosis, tuberculosis, or diseases other than primary hpt known to cause hypercalcemia * history of familial hypocalciuric hypercalcemia (fhh) * uncontrolled diabetes, as defined by hemoglobin a1c (hba1c) ≥ 8.0 * gastrointestinal disorder that may be associated with impaired absorption of orally administered medications * inability to swallow tablets similar in size to an aspirin tablet * known sensitivity to products administered during the study * previous participation as a subject in this study (ie, withdrawn early) or a prior study involving amg 073 administration * enrolled in, or not yet completed at least 28 days since ending other investigational device or drug trial(s) * psychiatric disorder that would interfere with understanding and giving informed consent or compliance with protocol requirements * any other condition that might reduce the chance of obtaining data (ie, known poor compliance) required by the protocol or that might compromise the ability to give truly informed consent